Pseudomonas aeruginosa is an opportunistic pathogen which poses a major threat to immunocompromised patients, burn victims, and cystic fibrosis (CF) patients. More than 90% of the mortality among CF patients is caused by lung infection with P. aeruginosa. Saiman et al., 1996, Clin Infect Dis. 23 (3): 532-7; Shawar et al., 1999, Antimicrob Agents Chemother. 43 (12): 2877-80. CF patients acquire P. aeruginosa infection from the environment at an early age. Repeated treatment with various antibiotics selects for multi-drug resistant strains. Alonso et al., 1999, Microbiology, 145 (Pt 10): 2857-62.
A number of mechanisms by which bacteria become resistant to antibiotics are known. Among these are enzymatic inactivation of the drug, alteration of drug target sites, development of bypass pathways around drug targets, and reduction in cell-wall membrane permeability. While most types of drug resistance are antibiotic-specific, membrane permeability reduction usually results in a multi-drug resistant phenotype. Reduced membrane permeability is common among clinical isolates of P. aeruginosa. Indeed, the vast majority of CF isolates exhibit reduced membrane permeability and a multi-drug resistant phenotype. Burns et al., 1999, J Infect Dis. 179 (5):1190-6; Shawar et al., supra. Although many of the molecular mechanisms underlying specific antibiotic resistance are well known, they remain poorly understood in multi-drug resistance.